Trophoblast glycoprotein (TPBG) is a leucine-rich transmembrane glycoprotein involved in cell adhesion. In adults this protein is highly expressed in many tumor cells and is associated with poor clinical outcome in numerous cancers.
Antibodies binding to TPBG (also referred to as “5T4”) are, e.g. disclosed in Shaw et al. (2002) Biochem. J. 363: 137-45 and WO98/55607. Those documents disclose antibody “H8”, which specifically binds to a conformational epitope of TPBG. Amino acid sequences of original murine H8 antibody and of a humanized version of H8 antibody are disclosed in WO 2006/031653.
Further antibodies binding to TPBG are, e.g. disclosed in Woods et al. (2002) Biochem. J. 366: 353-65 (which discloses a rat monoclonal antibody) and U.S. Pat. No. 5,869,053 (which discloses a mouse monoclonal antibody).
Further antibodies binding to TPGB are, e.g. disclosed and characterized in WO 2007/106744, referred to as antibodies A1, A2 and A3.
Therapeutic use of antibodies binding to TPBG in treatment of cancer is, e.g., disclosed in Myers et al. (2002) Cancer Gene Ther. 9: 884-896, Shaw et al. (2000) Biochim Biophys. Acta. 1524: 238-246; and US 2003/0018004, disclosing that anti-TPBG antibody antibody sequences fused to the human IgG1 constant domain or to the extracellular domain of murine B7.1 induces cytolysis of TPBG-expressing tumor cell lines. A phase I clinical trial using PNU-214936, a murine Fab fragment of a monoclonal anti-TPGB antibody fused to a mutated superantigen staphylococcal enterocytotoxin A (SEA), showed limited toxicity and some anti-tumor response (Cheng et al. (2004) J. Clin. Oncol. 22(4):602-9).